miR-150-Mediated Foxo1 Regulation Programs CD8+ T Cell Differentiation

Young Ho Ban, Se Chan Oh, Sang Hwan Seo, Seok Min Kim, In Pyo Choi, Philip D. Greenberg, Jun Chang, Tae Don Kim, Sang Jun Ha

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8+ T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8+ T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8+ T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8+ T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8+ T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics.

Original languageEnglish
Pages (from-to)2598-2611
Number of pages14
JournalCell Reports
Volume20
Issue number11
DOIs
StatePublished - 12 Sep 2017

Keywords

  • acute
  • CD8
  • differentiation
  • Foxo1
  • infection
  • LCMV
  • memory
  • miR-150
  • primary immune response
  • recall

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